The space environment is incredibly hostile, and humans are vulnerable in such conditions. Astronauts encounter various stress factors during a space journey, including radiation, microgravity, forceful acceleration during launch, altered magnetic fields, and confinement. These stressors significantly impact the human body homeostasis, leading to physio-pathological adaptations, loss of bone density, muscle atrophy, cardiovascular deconditioning, alterations in liver function, vestibular adaptations, and immune system dysregulation. These alterations can potentially influence drug pharmacokinetics and pharmacodynamics, affecting the efficacy and safety of medications administered to astronauts. Due to the limited number of studies on pharmaceuticals conducted in microgravity conditions, it’s challenging to assess the effectiveness and stability of these medications during spaceflight. The objective of the present work is to compare the state-of-the-art knowledge on PK/PD changes and factors likely to affect them during spaceflight, with the subjective perception of the problem by a collection of separate interviews conducted with seven experts in the field. The interviewees were chosen as “experts,” i.e., representatives in a specific discipline, who possess knowledge and experience in space pharmacology, physiology, or biology. Thus, our panel included astronauts, space surgeons, and scientists aiming to bridge the lack of experimental data in the literature. Each interview explores assorted aspects of space physiology and pharmacology, including drug use and storage onboard the ISS; notable consideration has arisen regarding the current research gaps and future space expeditions. All the interviews were held remotely using online conferencing software. None of the interviewees could provide a comprehensive overview regarding potential changes in drugs PK/PD in microgravity conditions. Further, any medication brought on board (whether as part of an astronaut’s medi Astronauts encounter various stress factors during a space journey, including radiation, microgravity, forceful acceleration during launch, altered magnetic fields, and con finement. These stressors signi ficantly impact the human body homeostasis, leading to physio-pathological adaptations, loss of bone density, muscle atrophy, cardiovascular deconditioning, alterations in liver function, vestibular adaptations, and immune system dysregulation. These alterations can potentially in fluence drug pharmacokinetics and pharmacodynamics, affecting the ef ficacy and safety of medications administered to astronauts. Frontiers in Space Technologies frontiersin.org01 TYPE Original Research PUBLISHED 18 October 2024 DOI 10.3389/frspt.2024.1456614 astronauts would be bene ficial for developing personalized pharmacological countermeasures for each astronaut and anticipating expected drug metabolism changes during space missions. KEYWORDS space environment, astronauts, microgravity, metabolism, pharmacokinetics, pharmacodynamics, pharmacogenetics 1 Introduction Human health faces signi ficant risks in the context of space travel. Astronauts encounter various stress factors during a space journey, including cosmic radiations, microgravity, strong acceleration during launch, altered magnetic fields, mechanical vibrations, pressure changes, close environment, isolation, and distance from Earth. In addition, the human body shifts dynamically across different time points, including pre- flight training, launch, extravehicular activity (EVA), and post- flight recovery ( Cope et al., 2022 ; Demontis et al., 2017 ). Speci fically, the questions asked included: 22 questions on medical issues and related pharmacological countermeasures; 14 questions regarding the main pharmacological issues/gaps (includ ing potential PK/PD alterations, drug side effects, polypharmacy, drug-drug interactions, drug-food interactions, drug formulations, radiation protection, and pharmacological studies in space); 13 questions on future perspectives and the role of pharmacological therapy in upcoming space missions; 9 questions regarding drug usage onboard the ISS (including pre- and post- flight periods); 6 questions dedicated to the personal astronaut experience onboard the ISS; 5 questions concerning the storage and management of medications onboard the ISS; 5 questions concerning the outcomes of research conducted by the interviewees.  Monitoring of medication usage on board is insuf ficient and this highlights the importance of the pharmacist ’s role within the space medical team.  ESA and NASA have adopted two different approaches regarding the medical kits for future missions (to the Moon or Mars). The perspectives provided by m ultiple researchers in the field, along with the direct testimony of an astronaut, aim to raise awareness of the scienti fic community toward a deeper focus on the topic of space pharmacology, including the use and management of drugs in space. Nonetheless, asking for a pharmacist ’s advice regarding this matter could warn the astronaut about the potential risks of using two medications –such as Zolpidem and Zaleplon - on the same night. Zolpidem and zaleplon are short-acting non- benzodiazepine sleep aids ( Rang et al., 2016 ; Lemke et al., 2013 ), better known as Z-agents; they act binding to GABA-A, but in a more speci fic fashion as compared to benzodiazepines. In this regard, the astronaut stated: “I didn ’t experience anything that had to do with pressure drops, but I did have a serious ... let’s call it instability problem, with vomiting and nausea. [ ... ]” (Q. 8). In this case, the astronaut did not experience any issues with OI, but upon returning to planet Earth, stability problems emerged, likely linked to vestibular SIC. Nonetheless, OI and stability issues upon re-entry to Earth pose many difficulties. Currently, a medical team is in place to assist astronauts upon landing.